The ability of the mammalian stomach to maintain pH and electrical gradients may be impaired in patients with both benign gastric ulcer disease and acute hemorrhagic gastritis. In the present proposal, assessment of this gastric mucosal barrier (GMB) will be accomplished in dog and primate by determining (1) net water and ion fluxes, (2) bidirectional ion fluxes, (3) absorption of C14-mannitol as a measure of mucosal pore area, (4) electrical potential difference, and (5) aminopyrine clearance as a measure of mucosal nutrient blood flow. Problems to be assessed include: (1) the effect, in vivo, of alterations in blood flow on the GMB, (2) the effect of alpha adrenergic blockade or stimulation on bile acid induced damage to the GMB, (3) the effect of sepsis on the GMB, (4) the relative efficacy of bile acids in different physical states in initiating damage to the GMB, (5) the effect of chronic disruption of the GMB on mucosal histology and function, (6) the role of preexistent atrophic gastritis in ulcerogenesis, and (7) the role of adenine nucleotides and certain endogenous humoral agents in maintaining a normal GMB.